Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease

• Main Authors: Alvarez Victoria, Coto Eliecer, Harrison Rachel, Kehoe Patrick G, Brown Kristelle, Wilcock Gordon K, Heun Reinhard, Kölsch Heike, Schuur Maaike, Aulchenko Yurii S, Lehmann Michael G, Cortina-Borja Mario, Arias-Vásquez Alejandro, Belbin Olivia, Hammond Naomi, van Duijn Cornelia M, Combarros Onofre, Deloukas Panos, Mateo Ignacio, Gwilliam Rhian, Morgan Kevin, Warden Donald R, Smith A David, Lehmann Donald J
• Format: Article
• Language: English
• Published: BMC 2009-08-01
• Series: Journal of Neuroinflammation
• Online Access: http://www.jneuroinflammation.com/content/6/1/22

<p>Abstract</p> <p>Background</p> <p>Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: <it>IL6</it>), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: <it>IL10</it>).</p> <p>Methods</p> <p>We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.</p> <p>Results</p> <p>We replicated the interaction. For <it>IL6 </it>rs2069837 AA × <it>IL10 </it>rs1800871 CC, the synergy factor (<it>SF</it>) was 1.63 (95% confidence interval: 1.10–2.41, <it>p </it>= 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (<it>APOE</it>ε4) genotype. Our results are consistent between North Europe (<it>SF </it>= 1.7, <it>p </it>= 0.03) and North Spain (<it>SF </it>= 2.0, <it>p </it>= 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.</p> <p>Conclusion</p> <p>We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.</p>